Transcript Document 124017

Lecture 6
General medicine_3rd semester
DEVELOPMENT OF URINARY SYSTEM AND
OVERVIEW OF ITS CONGENITAL MALFORMATION
DEVELOPMENT OF REPRODUCTIVE SYSTEM:
INDIFFERENT STAGE
DEVELOPMENT OF INTERNAL AND EXTERNAL
SEXUAL ORGANS
OVERVIEW OF MOST IMPORTANT CONGENITAL
MALFORMATIONS
Introduction
the urinary system and internal sexual
organs develop from the intermediate
mesoderm or nephrotomes
a part of the third germ layer
interposed between the axial mesoderm or
somites and lateral mesoderm
the intermediate mesoderm extends along
the entire length of the dorsal body wall of
the embryo
it soon loses connection with somites
and fuses to form the nephrogenic cords
on each side of the primitive aorta
the cords rapidly grow, become larger and
produce bilateral longitudinal bulges
called the urogenital ridges
a medial side of each ridge is then separated from
the surrounding and is called as
the gonadal ridge (see the next chapter)
DEVELOPMENT OF KIDNEYS, URETERS, BLADDER,
AND URETHRA
in the human, three sets of excretory organs develop:
the pronephros (-oi) - "forkidney" - is rudimentary and nonfunctional; forkidney is
analogous to the kidney of some primitive fishes,
the mesonephros (-oi) -" midkidney" - is analogous to kidney of fishes and larval stages
of amphibia amphibians; in human embryos, midkidney is in function for a short
time and then undergoes involution
the metanephros (-oi) - "hindkidney" or permanent kidney, it begins to produce urine
in fetuses aged 11 to 13 weeks
Pronephros (oi)
occurs early in the fourth week in the cervical region on each side
it consists of a few solid cell clusters, rarely short pronephric tubules and the pronephric
duct, which runs caudally and opens into the cloaca
the pronephros soon degenerates, but most of both pronephric ducts are utilized by the
midkidney as mesonephric or Wolffian duct
Mesonephros (oi)
develops later in the 4th week caudal to the pronephros in C6 to L3 region
initially, solid nephrogenic cord (blastema) divides into 40 - 50 mesodermal cell clusters within them lumina
develop - mesonephric vesicles arise
mesonephric vesicles grow into S-shaped mesonephric tubules whose laterally ends become
continuous with the mesonephric duct or Wolffian duct
the medial end of each tubule expands and transforms into
the Bowman´s capsule (capilary loops of the glomerulus are
deriving from the mesonephric artery)
the capsule with glomerulus form a mesonephric corpuscle
together
cervical and thoracical parts of mesonephroi rapidly degenerate
the lumbar part consisting of a few mesonephric tubules
and mesonephric duct persists and is involved in development
of genital ducts in males (ductuli efferentes, ductus deferens and ductus
ejaculatorius) or vestigial remnants in females (epoophoron and paroophoron)
Metanephros (oi)
"hindkidney" or permanent kidney begins to develop early in the 5th week
two different sources:
 the ureteric bud or metanephric diverticulum, which gives rise to the ureter, pelvis,
major and minor calyces and system of papillary ducts and collecting tubules
 the metanephrogenic blastema or metanephric mesoderm = a caudal part of the
nephrogenic cord extending between L4 to S1 - it gives rise to the nephrons
the ureteric bud is a dorsal outgrowth
of the mesonephric duct near its entry into
the cloaca
the bud then extends dorsocranially, penetrates
the metanephric mesoderm and divides it into
cell clusters, located near blind ends of the
collecting tubules
clusters of mesodermal cells become
metanephric vesicles that are later
transformed into metanephric tubules
the proximal part of each tubule becomes
dilated
and forms the Bowman´s capsule of a renal
corpuscle, while
the distal end contacts the respective collecting
tubule and both tubules become soon confluent
the remaining part of the metanephric tubule
undergoes continual lengthening and
gradually differentiates into definitive segments
of the uriniferous tubule
the proximal tubule, the loop of Henle, and
the distal tubule
Positional changes of the kidneys
kidneys develop low in the pelvis
from the 2nd trimester, they gradually come to lie in the abdomen
the migration of kidneys is mainly resulted from growth of the embryo´s body
caudal to the kidneys
ascensus renis
Development of renal pelvis and ureter
both derive from the distal part of the ureteric bud
Development of bladder and urethra
both organs develop from the ventral part of the cloaca
the cloaca is the most caudal part of the gut which is ventrally sealed off by a membrane composed of the
ectoderm and endoderm - known as the cloacal membrane
cranially, the cloaca continues as the allantois that enters the connecting stalk
in higher vertebrates including the human, the cloaca soon divides with the urorectal septum
(oriented frontally) into 2 portions :
- the anorectal canal situated dorsally - rectum,
- the primitive urogenital sinus situated ventrally - bladder + urethra.
the caudal part of the urorectal septum then fuses with the cloacal membrane: a part covering anorectal
canal is the anal membrane, a part covering the primitive urogenital sinus is the urogenital
membrane
the urogenital sinus includes three parts:
 vesical segment (presumptive bladder - there is a wide cranial part
 pelvic segment - middle narrow
 phallic segment - it appears wide
the vesical segment develops into the definitive bladder - in both sexes
the pelvic segment becomes
the definitive urethra in females
but
the phallic segment of the urogenital sinus becomes
the vestibule of the vagina in females
but
the prostatic urethra in males
the penile urethra in males
CONGENITAL MALFORMATIONS OF KIDNEYS AND
URETERS
Renal agenesis = absence of a kidney
it results from failure of the ureteric bud to growout and is accompanied with an absence of
the ureter
it may be uni- or bilateral
(unilateral agenesis is characterised by compensatory hypertrophy of the kidney that is present; bilateral
agenesis is incompatible with survival after birth)
incidence is about 2 (3) per 10 000; is more frequent in males than females (3:1)
clinically, it is always accompanied by oligohydramnios which results from failure of urine
production
Pelvic kidney = a kidney (s) is
located in pelvis,
this malformation results from failure
of the kidney to ascend
Horshoe kidney - both kidneys are fused
at their inferior poles and located in pelvis
(failure of kidneys ascend)
horshoe kidney is often symptomless and
occurs 1 per 600 live birth.
Polycystic kidney disease = hereditary disease characterised by that one or both kidneys
contain numerous small, medium - sized or large urine-filled cysts inhibiting its normal
function
polycystic kidney disease may be uni- or bi-lateral
bilateral p. k. d. has almost bad prognosis because it is incompatible with survival after birth
P. k. d. is believed to result from failure of collecting tubules and uriniferous tubules to join
up.
Polycystic kidney disease occurs in two hereditary forms. One is autosomal recessive or infantile, the other is autosomal
dominant, or adult.
Duplication of the ureter ureter duplex
and bifid ureter (ureter fissus)
DEVELOPMENT OF INTERNAL SEXUAL ORGANS
(gonads and ducts)
the early genital system is similar in both sexes, and this initial period is referred to as the indifferent
stage
it lasts approximately up to the first half of the 3rd month (10th week) of the fetal development
the
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stage is characterized by presence of 3 embryonic organs:
the indifferent gonad anlage
the mesonephric duct (Wolffian duct) + remnants of mesonephric tubules
the paramesonephric duct (Müllerian duct)
The indifferent gonad anlage lies within the gonadal (genital) ridge that is bilateral
organ
the gonadal ridge is a mesenchymal structure located on the medial side of the mesonephros
(urogenital ridge); initially is of the same length as the mesonephros, but portion from C6 to
L2 then rapidly degenerates, the caudal part (S1-S3) is transformed in the gubernaculum
a segment of the ridge extending between L3-L5 forms an anlage of the future
gonad and is early invaded with primordial germ cells (PGCs)
PGCs differentiate outside the body (in the yolk sac and the gut) and migrate into indifferent
gonad anlage by week 6
a surface of the future gonad is covered with a coelomic epithelium that thickens and
proliferates in the underlying mesenchyma in the form finger-like epithelial cords - called
primary sex cord
the indifferent gonad consists of an outer cortex and an inner medulla
The mesonephric duct and
remnants of mesonephric
tubules - persist from the
"midkidney" stage.
The paramesonephric duct is primitive genital duct that develops from the longitudinal
invagination of coelomic epithelium covering the lateral aspect of the genital ridge (on each
side)
the proximal end opens into the coelomic, future peritoneal, cavity, the caudal end runs
parallel to the mesonephric duct
in the small pelvis ducts cross ventral to the mesonephric ducts, come together in the
midline, and fuse into Y-shaped uterovaginal primordium or canal
(the primordium projects into the dorsal wall of the urogenital sinus and produces an elevation, called the
sinus tubercle)
if the indifferent gonad anlage will develop in the testis or ovary,
depends on the presence or absence of a Y chromosome
in presence of a Y
chromosome, the
gonad anlage
differentiates
into the
testis
the absence
of a Y
chromosome
results in
differentiation
of the
ovary
Development of testes
in embryos with a Y chromosome, the primary sex cords lose their connections with the
coelomic epithelium and persist as the testicular cords that soon undergoe transformation
into the seminiferous tubules
cells of the seminiferous tubules differentiate in the Sertoli cells, PGCs give rise to
spermatogonia
the interstitial (Leydig) cells arise from the mesenchyma of indifferent gonad anlage
the tunica albuginea is developed early as a condensation of the mesenchyma lying between
the coelomic epithelium and seminiferous tubules
Development of ovaries
in embryos lacking a Y chromosome, the primary sex cords degenerate and migrate in the
medulla in which form a rudimentary rete ovarii
the superficial coelomic epithelium sends off new sex cord, called secondary or cortical
sex cords
these separate from it and are differentiated into the follicular cells which, in association
with PGCs, form the primordial ovarian follicles
the mesenchyma extending between the surface epithelium and ovarian follicles gives rise to
the thin fibrous capsule - tunica albuginea
Descent of testis
Descent of ovary
by the 28th week
from the peritoneal cavity to the scrotum
to the small pelvis
Development of genital ducts
in the presence of a Y chromosome
male sex
are transformed into efferent
ductuli (ductuli efferentes)
becomes the ductus
epididymidis, ductus
deferens and ejaculatory
duct
regresses (rarely it may give
rise to a rudimentary
appendix testis)
regresses (rarely utriculus
prostaticus)
indifferent stage
remnants of mesophric
tubules
the mesonephric
(Wolffian) duct
the paramesonephric
duct
unfused portion
the uterovaginal
primordium
the absence of a Y chromosome
female sex
regress
(tubules may persist as
epoophoron and
paroophoron)
regresses
cranial end of the duct may
persists as appendix
vesiculosa, caudal part as
the duct of Gartner
the oviduct (fallopian tube)
the uterus + cranial part
of the vagina
Derivatives of the paramesonephric duct:
Development of external genitalia - indifferent stage
external genitalia undergoe the indifferent stage similar as gonads and genital ducts
the indifferent stage is characterised by
 a genital tubercle - is situated at the cranial end of the cloacal membrane
it rapidly grows and elongates to form the phallus
 the cloacal (urogenital) folds - are paired and demarcate the urogenital
orifice
 the labioscrotal swellings - are located laterally to the urogenital folds on
each side
male sex
indifferent stage
female sex
the phallus
gives rise to the penis
grows slowly and is
transformed in the
clitoris
urogenital folds
fuse in midline and close
the urogenital orifice – the
cavernous urethra
grow toward each other
and fuse to form the
scrotum
do not fuse and form the
labia minora
labioscrotal
swellings
remain unfused similar to
folds and form the labia
majora
the male sex
the female sex
OVERVIEW OF CONGENITAL MALFORMATIONS OF GENITAL ORGANS
because an early embryo has the potential to develop as either a male or a
female, errors in sex development may result in intermediate sex, a condition
known as intersexuality, or hermaphroditism
a person with ambiguous external genitalia is called intersex, or a
hermaphrodite
true hermaphrodites - have both ovarian and testicular tissue (ovotestis)
occur extremely rare
false hermaphrodites or pseudohermaphrodites - occur about once in
25,000 birth
two forms are distinguished:
- female pseudohermaphrodites - have 46,XX karyotype and ovaries, but external
genitalia resemble masculine genitalia (hypertrophied clitoris, the labia majora are
partially fused, the persistent urogenital sinus)
malformation mostly occurs in the form of the adrenogenital syndrome, resulting
from congenital virilizing adrenal hyperplazia
- male pseudohermaphrodites - 46,XY constitution, they have testes, but external
genitalia resemble in various degree of female genitalia
is caused by inadequate production of testosterone, androgen receptor disorders, 5-a
reductase deficiency or MDIF deficiency
Malformations occuring in males:
cryptorchidism - (undescended testes) - is found in one in three premature male babies or
in one in 30 full-term males
testes are retained in the abdominal cavity or in the inguinal canal
sterility is resulting if the condition persists to the puberty
anomaly may repair spontaneously, if not, the surgical treatment must follows
congenital inguinal hernia - occurs in the case of unclosed processus vaginalis, which
connects the tunica vaginalis with the peritoneal cavity
if the abdominal pressure is increased, then intestinal loops herniate through it into the
scrotum (rarely labium majus), congenital inguinal hernia is often accompanied with
cryptorchidism
hydrocele - if the abdominal end of the processus vaginalis remains open, the peritoneal
fluid passes into it and forms a hydrocele of the testis and spermatic cord
hypospadias - a malformation in which the external urethral orifice is on the ventral
surface of the penis instead of at the tip of the glans
it occurs one in about every 300 males
4 types of hypospadias: glandular, penile, penoscrotal, and perineal
(the glandular and penile constitute about 80 per cent of cases)
epispadias - is a malformation in which the urethra opens on the dorsal aspect of the penis
and is often associated with extrophy of the bladder
it occurs once in about 30,000 male infants
agenesis of the penis - extremely rare malformation results from failure of the genital tubercle to develop
bifid penis and double penis - very rare - distal part of the penis is divided into two portions, it results from failure of
fusion of two parts of the genital tubercle (if two genital tubercles do not fuse - it develops double penis)
micropenis - the penis is so small that it is almost hidden by the suprapubic pad of fat ; it is usually associated
with hypopituitarism and hormonal deficiency of the fetal testes
Malformations occuring in females:
ectopic ovary - the ovary shows abnormal location, rare
uterovaginal malformations - result from
(1) improper fusion of both paramesonephric ducts
(2) incomplete development of one paramesonephric duct
(3) failure of parts of one or both ducts to develop
(4) incomplete canalization of the vaginal plate
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double uterus (uterus didelphys)
bicornuate uterus
unicornuate uterus with one uterine tube
absence of the uterus
absence of the vagina - once in about every
4000 females
vaginal atresia - results from failure of
canalization of the vaginal plate
anorectal agenesis and fistulas - the rectum ends well above the anal canal and is
connected to the vagina with a fistula (rectovaginal fistula)
is the most common type of anorectal malformations